P961: CILTACABTAGENE AUTOLEUCEL, A BCMA-DIRECTED CAR-T CELL THERAPY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: 2-YEAR POST LPI RESULTS FROM THE PHASE 1B/2 CARTITUDE-1 STUDY
Authors: Y. Lin, T. Martin, J. G. Berdeja, A. Jakubowiak, M. Agha, A. D. Cohen, A. Deol, M. Htut, A. Lesokhin, N. C. Munshi, E. O’Donnell, C. C. Jackson, T.-M. Yeh, A. Banerjee, E. Zudaire, D. Madduri, C. Zhou, L. Pacaud, S. Z. Usmani, S. Jagannath
Journal: HemaSphere (2022)

Background: The phase 1b/2 CARTITUDE-1 study (NCT03548207) reported early, deep, and durable responses with ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen (BCMA)–targeting single-domain antibodies, in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). At a median follow-up of ~1 year, the overall response rate (ORR) was 97%, with 67% of patients achieving stringent complete response (sCR). Progression-free survival (PFS) and overall survival (OS) rates at 1 year were 77% and 89%, respectively. Aims: To report updated 2-year post last patient in (LPI) results (total median follow-up of ~30 months). CARTITUDE-1 results at a median follow-up of 21.7 months are reported here. Methods: All patients provided informed consent. Patients with RRMM had received ≥3 prior lines of therapy (LOT) or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Patients had received a PI, IMiD, and anti-CD38 antibody. After apheresis, bridging therapy was allowed. A single cilta-cel infusion was administered at a target dose of 0.75×106 CAR+ viable T cells/kg 5-7 days after lymphodepletion. The primary objectives were to evaluate the safety and efficacy of cilta-cel. Response assessments were based on International Myeloma Working Group criteria by independent review committee. Minimal residual disease (MRD) negativity at 10-5 was assessed by next-generation sequencing. Results: 97 patients (male: 59%; median age: 61 years) received cilta-cel as of July 22, 2021. The median number of prior LOT was 6 (range: 3-18). 84% of patients were penta-drug exposed, 88% were triple-class refractory, 42% were penta-drug refractory, and 99% were refractory to their last LOT. The ORR was 97.9% (95% CI: 92.7-99.7), with 94.9% of patients achieving very good partial response and 82.5% achieving sCR. Median time to first response was 1.0 month, median time to best response was 2.6 months, and median time to ≥CR was 2.9 months. Median duration of response was not reached. Among 61 MRD-evaluable patients, 92% were MRD negative at 10-5, which was sustained in 44% of patients (27/61) for ≥6 months and in 18% of patients (11/61) for ≥12 months. Median PFS and OS were not reached. The 2-year PFS rate was 60.5% (95% CI: 48.5-70.4) overall. The 2-year PFS rate was 91% for patients with sustained MRD negativity ≥6 months and 100% for those with sustained MRD negativity ≥12 months. No new safety signals or new cases of CAR-T cell neurotoxicity, movement/neurocognitive treatment-emergent adverse events, or treatment-related deaths were reported since 1-year median follow-up. Over a median follow-up of ~2-years, 15 second primary malignancies occurred in 11 patients. Summary/Conclusion: A single cilta-cel infusion resulted in deepening and durable responses in heavily pretreated patients with RRMM at a median follow-up of ~2 years. The safety profile was manageable. Follow-up in CARTITUDE-1 is ongoing. We will present landmark 2-year post LPI data, with ~8 months of additional follow-up (~30 months total median follow-up). Cilta-cel is also being evaluated in earlier LOT and outpatient settings across the CARTITUDE program, including NCT04133636, NCT04181827, NCT04923893.